The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians

BMC Medical Genetics

Volumn 7, Issue , 2006, Pages

  Freathy, Rachel M ^a   Weedon, Michael N ^a   Melzer, David ^a   Shields, Beverley ^a   Hitman, Graham A ^b   Walker, Mark ^c   McCarthy, Mark I ^d   Hattersley, Andrew T ^a   Frayling, Timothy M ^a  

^a PENINSULA MEDICAL SCHOOL   (United Kingdom)

^b QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^c NEWCASTLE UNIVERSITY   (United Kingdom)

^d UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIDIABETIC AGENT; GLUCOSE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HORMONE; INSULIN; KLOTHO; LOW DENSITY LIPOPROTEIN CHOLESTEROL; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

ADULT; ALLELE; ARTICLE; CASE CONTROL STUDY; CAUCASIAN; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DIET RESTRICTION; FAMILY STUDY; FEMALE; GENE FREQUENCY; GENE TRANSFER; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; GENOTYPE; GLUCOSE BLOOD LEVEL; HUMAN; INSULIN BLOOD LEVEL; MAJOR CLINICAL STUDY; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; PROTEIN FUNCTION; QUANTITATIVE ANALYSIS; RISK ASSESSMENT; RISK FACTOR; SAMPLE SIZE; SINGLE NUCLEOTIDE POLYMORPHISM; TRIACYLGLYCEROL BLOOD LEVEL; UNITED KINGDOM;

ADULT; CASE-CONTROL STUDIES; DIABETES MELLITUS, TYPE 2; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; GENE FREQUENCY; GENETIC PREDISPOSITION TO DISEASE; GLUCURONIDASE; GREAT BRITAIN; HUMANS; MALE; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 33746937807     PISSN: 14712350     EISSN: 14712350     Source Type: Journal    
DOI: 10.1186/1471-2350-7-51     Document Type: Article

References (21)

1. Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, Shimomura I, Takayama Y, Herz J, Kahn CR, Rosenblatt KP, Kuro-o M: Suppression of aging in mice by the hormone Klotho. Science 2005, 309(5742):1829-1833.
2. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI: Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997, 390(6655):45-51.
3. Utsugi T, Ohno T, Ohyama Y, Uchiyama T, Saito Y, Matsumura Y, Aizawa H, Itoh H, Kurabayashi M, Kawazu S, Tomono S, Oka Y, Suga T, Kuro-o M, Nabeshima Y, Nagai R: Decreased insulin production and increased insulin sensitivity in the klotho mutant mouse, a novel animal model for human aging. Metabolism 2000, 49(9):1118-1123.
4. Arking DE, Krebsova A, Macek MS, Macek MJ, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I, Dietz HC: Association of human aging with a functional variant of klotho. Proc Natl Acad Sci U S A 2002, 99(2):856-861.
5. Arking DE, Atzmon G, Arking A, Barzilai N, Dietz HC: Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity. Circ Res 2005, 96(4):412-418.
6. Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y: Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun 1998, 242(3):626-630.
7. Arking DE, Becker DM, Yanek LR, Fallin D, Judge DP, Moy TF, Becker LC, Dietz HC: KLOTHO allele status and the risk of early-onset occult coronary artery disease. Am J Hum Genet 2003, 72(5):1154-1161.
8. Low AF, O'Donnell CJ, Kathiresan S, Everett B, Chae CU, Shaw SY, Ellinor PT, MacRae CA: Aging syndrome genes and premature coronary artery disease. BMC Med Genet 2005, 6:38.
9. Report of a WHO Consultation: Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Part 1: Diagnosis and Classification of Diabetes Mellitus. World Health Organisation, Department of Noncommunicable Disease Surveillance, Geneva 1999.
10. Weedon MN, Owen KR, Shields B, Hitman G, Walker M, McCarthy MI, Love-Gregory LD, Permutt MA, Hattersley AT, Frayling TM: Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population. Diabetes 2004, 53(11):3002-3006.
11. Weedon MN, Owen KR, Shields B, Hitman G, Walker M, McCarthy MI, Hattersley AT, Frayling TM: A Large-Scale Association Analysis of Common Variation of the HNFI {alpha} Gene With Type 2 Diabetes in the U.K. Caucasian Population. Diabetes 2005, 54(8):2487-2491.
12. Wiltshire S, Hattersley AT, Hitman GA, Walker M, Levy JC, Sampson M, O'Rahilly S, Frayling TM, Bell JI, Lathrop GM, Bennett A, Dhillon R, Fletcher C, Groves CJ, Jones E, Prestwich P, Simecek N, Rao PV, Wishart M, Foxon R, Bottazzo GF, Howell S, Smedley D, Cardon LR, Menzel S, McCarthy MI: A genomewide scan for loci predisposing to type 2 diabetes in a U.K. population (the Diabetes UK Warren 2 Repository): analysis of 573 pedigrees provides independent replication of a susceptibility locus on chromosome 1q. Am J Hum Genet 2001, 69(3):553-569.
13. Minton JA, Hattersley AT, Owen K, McCarthy MI, Walker M, Latif F, Barrett T, Frayling TM: Association studies of genetic variation in the WFSI gene and type 2 diabetes in U.K. populations. Diabetes 2002, 51(4):1287-1290.
14. Knight B, Shields BM, Hattersley AT: The Exeter Family Study of Childhood Health (EFSOCH): study protocol and methodology. Paediatr Perinat Epidemiol 2006, 20(2):172-179.
15. Frayling TM, Walker M, McCarthy MI, Evans JC, Allen LIS, Lynn S, Ayres S, Millauer B, Turner C, Turner RC, Sampson MJ, Hitman GA, Ellard S, Hattersley AT: Parent-offspring Trios: a resource to facilitate the identification of Type 2 diabetes genes. Diabetes 1999, 48:2475-2479.
16. Gloyn AL, Weedon MN, Owen KR, Turner MJ, Knight BA, Hitman G, Walker M, Levy JC, Sampson M, Halford S, McCarthy MI, Hattersley AT, Frayling TM: Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel sub-units Kir6.2 (KCNJII) and SURI (ABCC8) confirm that the KCNJII E23K variant is associated with type 2 diabetes. Diabetes 2003, 52(2):568-572.
17. Zeggini E, Parkinson JR, Halford S, Owen KR, Walker M, Hitman GA, Levy JC, Sampson MJ, Frayling TM, Hattersley AT, McCarthy MI: Examining the relationships between the Pro12Ala variant in PPARG and Type 2 diabetes-related traits in UK samples. Diabet Med 2005, 22(12):1696-1700.
18. [http://www.kbioscience.co.uk]
19. Rabinowitz D, Laird N: A unified approach to adjusting association tests for population admixture with arbitrary pedigree structure and arbitrary missing marker information. Hum Hered 2000, 50(4):211-223.
20. Laird NM, Horvath S, Xu X: Implementing a unified approach to family-based tests of association. Genet Epidemiol 2000, 19 Suppl 1:S36-42.
21. Spielman RS, Ewens WJ: A sibship test for linkage in the presence of association: the sib transmission/disequilibrium test. Am J Hum Genet 1998, 62:450-458.